Compositions and methods for activating NRF2-dependent gene expression

Abstract

Embodiments are directed to a series of novel small molecule activators of NRF2 dependent gene expression that are evaluated in an effort to develop therapeutic methods against diseases with deregulated KEAP1-NRF2 signaling.

The invention claimed is: 
     
       1. A method for activating nuclear factor erythroid 2-related factor 2 (Nrf2) dependent gene expression by inhibiting phosphoglycerate kinase 1 (PGK1) in a subject in need thereof, comprising administering to the subject a PGK1 inhibitor having a structure selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
       2. A method for treating a subject having pulmonary fibrosis or acute lung injury comprising administering to the subject an activator of Nrf2 dependent gene having a structure selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
       3. The method of  claim 2 , wherein the subject has pulmonary fibrosis. 
     
     
       4. The method of  claim 2 , wherein the subject has acute lung injury.